Complex living interface-coordinated self-assembling materials (clicsam)

Abstract

Disclosed herein is a composition comprising a stimulated heterogeneous mammalian tissue interface cell aggregate that is capable of producing functional polarized tissue when administered to a subject in need thereof.

1 . A composition comprising a stimulated heterogeneous mammalian tissue interface cell aggregate that is capable of producing functional polarized tissue when administered to a subject in need thereof. 
     
     
         2 . The composition of  claim 1 , wherein the stimulated heterogeneous mammalian tissue interface cell aggregate is derived from an osseous tissue interface. 
     
     
         3 . The composition of  claim 2 , wherein the osseous tissue interface is a peri-cortical tissue interface, a peri-lamellar tissue interface, a peri-trabecular tissue interface, a cortico-cancellous tissue interface, or any combination thereof. 
     
     
         4 . The composition of  claim 2 , wherein the stimulated heterogeneous mammalian tissue interface cell aggregate comprises living core potent cellular entities and supportive entities. 
     
     
         5 . The composition of  claim 4 , wherein the living core potent cellular entities express RNA transcripts and/or polypeptides of one or more Leucine Rich Repeat Containing G Protein-Coupled Receptors selected from the group consisting of LGR4, LGR5, LGR6, and any combination thereof. 
     
     
         6 . The composition of  claim 4 , wherein the living core potent cellular entities express RNA transcripts and/or polypeptides of one or more of Pax 7, Pax 3, MyoD, Myf 5, or any combination thereof. 
     
     
         7 . The composition of  claim 2 , wherein the stimulated heterogeneous mammalian tissue interface cell aggregate exhibits increased expression levels of parathyroid hormone, TLR4, and/or thymidine phosphorylase compared to that observed in native osseous tissue. 
     
     
         8 . The composition of  claim 2 , wherein the functional polarized tissue shows decreased expression levels of one or more of IL2, MYOSIN2, ITGB5, and STAT3 compared to that observed in native osseous tissue. 
     
     
         8 . (canceled) 
     
     
         9 . The composition of  claim 4 , wherein the supportive entities comprise cellular populations, extracellular matrix elements, or any combination thereof, and optionally wherein the supportive entities comprise mesenchymal derived cellular populations. 
     
     
         10 . The composition of  claim 9 , wherein the extracellular matrix elements comprise one or more of hyaluronic acid, elastin, collagen, fibronectin, laminin, extracellular vesicles, enzymes, and glycoproteins. 
     
     
         11 . The composition of  claim 2 , further comprising a delivery substrate, wherein the delivery substrate comprises a scaffold. 
     
     
         12 . The composition of  claim 2 , wherein the stimulated heterogeneous mammalian tissue interface cell aggregate has a diameter of about 40 to about 250 μm. 
     
     
         13 . A kit comprising the composition of  claim 2  and instructions for use. 
     
     
         14 . A method for promoting tissue regeneration in a subject in need thereof comprising administering to the subject an effective amount of the composition of  claim 2 . 
     
     
         15 . A method for treating a subject in need of tissue repair comprising administering to the subject an effective amount of the composition of  claim 2 . 
     
     
         16 . The method of  claim 15 , wherein the subject is suffering from a degenerative bone disease or a bone fracture or break. 
     
     
         17 . A method for preparing the composition of  claim 2  comprising isolating at least a portion of a mammalian material interface to obtain a heterogeneous mammalian tissue interface cell aggregate, wherein the mammalian material interface comprises heterogeneous mammalian tissue interface cells; and stimulating the heterogeneous mammalian tissue interface cells. 
     
     
         18 . The method of  claim 17 , wherein stimulating comprises mechanical stimulation, chemical stimulation, enzymatic stimulation, energetic stimulation, electrical stimulation, biological stimulation, or any combination thereof. 
     
     
         19 . The method of  claim 18 , wherein chemical or biological stimulation comprises at least one of chemokine receptor binding, paracrine receptor binding, cell membrane alteration, cytoskeletal alteration, alteration of physiological gradients, addition of small molecules or addition of nucleotides and ribonucleotides. 
     
     
         20 . A method for treating a subject in need of tissue repair comprising administering to the subject an effective amount of a composition comprising a stimulated heterogeneous mammalian tissue interface cell aggregate that is capable of producing functional polarized tissue when administered to a subject in need thereof, wherein administration of the composition results in an increase in at least one of parathyroid hormone, TLR4, thymidine phosphorylase in the subject compared to that observed prior to administration.